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A winding road: One advanced practice provider’s journey in drug development and clinical trials
Editor’s note: HemOnc Today’s regular columns for advanced practice providers (APPs) tackle common issues APPs face, discuss day-to-day practice and regulatory concerns, and highlight research advances. To contribute to this column, contact Alexandra Todak at stodak@healio.com.
I have worked in the cancer research arena for the bulk of my adulthood.
Starting as a young graduate student in biochemistry, my goal was to develop a new antiestrogen for the treatment of breast cancer. I moved onto a postdoctoral fellowship, during which I had my first experience with patients — only they were the four-legged kind that would bite if you weren’t careful!
I spent several years in the preclinical evaluation of investigational agents in animal models. It was during this time that several pivotal events caused me to redirect my career path in a more clinical direction.
Fast forward a few years to my joining the phase 1 clinical trial team at Karmanos Cancer Institute in Detroit as research physician assistant — it is here where I found my niche for almost 15 years.
A career that nurtures my inner science nerd and allows me to take care of patients has been perfect for me. During my tenure here, I have had the privilege to grow and work with some amazing physicians, APPs, nurses, study coordinators, eligibility coordinators, data managers and, most importantly, patients.
Our program has proudly played a role in helping bring many investigational agents to market. We have done this by working together as team, with each of us playing an equally important role in the process. We all come to the oncology world via different paths but, ultimately, we all have the same goal — caring for patients and helping them live as long as they can with the best quality of life we can help them achieve.
Starting a clinical trial
Developing new therapeutic options allows us the greatest chance of success for improving patient outcomes.
To do this, clinical trials must be developed and run appropriately; this is a complex and team-based endeavor, and APPs can be involved in every step of the process.
Several individuals and groups are essential to a clinical trial team. Ultimately, all protocols begin with a sponsor, an individual or organization that takes responsibility for initiating and managing a clinical trial.
Typically, a sponsor does not actually conduct the trial but chooses clinical investigators to participate. A sponsor-investigator, on the other hand, takes on the responsibility as a clinical study sponsor and also conducts or oversees the clinical trial.
Each clinical trial also has a principal investigator (PI) who supervises all aspects of the clinical trial. PIs often are involved in developing the trial and writing the protocol.
Once the clinical trial protocol is written, it is submitted for several reviews before the entire team is built and patients are enrolled.
Initially, most protocols undergo an internal review at the institution where the trial will be conducted, followed by a review from an institutional review board/independent ethics committee (IRB/IEC) who evaluate the protocol to ensure the trial is ethical and that the rights of patients are protected.
IRBs/IECs can be institutionally based or independent from the clinical site. APPs can and should be a member of any of the committees involved in the approval process of a clinical trial.
I am sure the first reaction when you read the above statement is, “Where am I going to find the time in an already packed day?” I assure you — these committees are an incredible opportunity to learn from and interact with our colleagues on a whole different level. I have been an active participant in our protocol review committee for many years and it has been well worth the effort.
Admittedly, it was an uphill battle when I joined as the first APP ever on the committee. At first I was assigned the “simpler” tasks. With perseverance, however, that changed. Now, I am assigned all types of protocols and am often the main clinical reviewer presenting.
The clinical team
If a trial makes it through the review processes and is approved, the clinical team is assembled and eligible patients can be enrolled in the trial.
Sub-investigators and clinical research coordinators play key roles in the day-to-day onsite operation of the clinical trial.
Sub-investigators are designated and supervised by the PI to perform trial-related procedures and to make trial-related decisions but don’t accept primary responsibility for the study.
APPs who work in the clinical trial arena are often sub-investigators, responsible for the day-to-day care of trial patients. They help evaluate potential participants, often educating patients regarding treatment options and specific trials for which they may be eligible. An APP can be involved in the consenting process and determining if patients meets all inclusion and exclusion criteria for trial enrollment.
Another key role of the sub-investigator is evaluating and treating toxicities experienced by patients in the trial.
When an adverse event or serious adverse event occurs, PIs and sub-investigators attempt to determine if the toxicity was directly related to the investigational agent or was due to something else, such as the patient’s cancer or a comorbid condition. This is an extremely important decision, as the attribution of toxicity to an investigational agent may determine whether a drug continues to be developed.
Clinical research coordinators — also called trial coordinators, study coordinators and research coordinators — are responsible for most of the administrative responsibilities of a clinical trial on behalf of the PI.
They act as the primary liaison between the investigative site and sponsor. They also are responsible for managing data collection throughout the trial. They often assist the PI or sub-investigator with the informed consent process and educate the staff, health care providers and patients about the trial.
Data managers work closely with clinical research coordinators to prepare and enter trial-related data, and they provide up-to-date data to monitoring agencies.
Often, if the organization is small, all of the above roles are held by one or two individuals, and these often are APPs.
Once a clinical trial is underway, it is periodically monitored.
A clinical monitor — an individual who acts on the sponsor’s behalf to evaluate the progress of sites participating in the clinical trial — is responsible for ensuring that a study is being conducted in accordance with the protocol and good clinical practice guidelines.
Often, there is an internal data safety monitoring committee (DSMC) that also monitors the protocol to ensure patient safety. IRBs/IECs also periodically monitor each clinical trial. This is another area in which APPs can be involved, either through direct employment by the sponsor or as a member of the DSMC or IRB/IEC.
Being a member of our institution’s DSMC for over 13 years has taught me how careful a PI must be in evaluating every toxicity that a patient experiences on a clinical trial. Trials with too many unexpected or serious toxicities may be terminated if the risk to patients is determined to be too high.
Challenges and rewards
A successful clinical trial program works as a well-oiled machine, with each member of the team having equal importance and value.
Working in clinical trials, however — especially in the phase 1 arena — is not for every APP.
Attention to detail is extremely important. Evaluations must be done in the time frame designated by the study protocol. The amount of documentation required for patients on clinical trials is extensive. A simple clinic note for a return patient on a clinical trial can often mimic an initial history and physical.
The use of investigational drugs also can be challenging when physicians and APPs treat toxicities.
For example, there are times when a standard supportive care agent can’t be used because it is a prohibited by the trial due to potential drug-drug interactions. This may require a consult with a pharmacist or the sponsor, and this process can be time-consuming for patients and clinicians.
Such attention to detail, however, is a necessity to ensure the least amount of toxicity and best chance of the investigational agent to be effective.
Perhaps more specific to the phase 1 area, most patients enrolled in these trials eventually will succumb to their disease, often very quickly, as many times a clinical trial is their “last resort.”
An APP in this arena has to be comfortable with addressing end-of-life issues daily. He or she also must be comfortable with “the unknown,” as often little is known about the efficacies and toxicities of investigational agents.
The ability to play a role in providing patients with hope and access to agents that may not be available to the general population for years is a very rewarding part of my job. The privilege of caring for patients with cancer, many of whom are at the end of their lives, has been life-changing for me.
My patients have taught me to not wait to start ticking things off my bucket list. They have taught me to truly “not sweat the small stuff.”
I often start the day reminding myself that, even if I am having a challenging day, chances are the patient in the room I am entering is having a worse day.
My patients are at the hospital to be treated, and I am here to work. They are spending what may be their last days participating in a trial that may be of little benefit to them, yet how often do I hear them say, “It may help someone else.”
The altruism of our patients is overwhelming and affirms my choice to work in clinical trials.
Seeing a patient able to live longer and reach a goal she or he never thought they would is an overwhelming reward.
For more information:
Mary Jo Pilat, PhD, MS, PA-C, CCRP, is assistant professor-clinical at Eugene Applebaum College of Pharmacy and Health Sciences of Wayne State University. She practices clinically as Research PA at the Karmanos Cancer Institute. She also is a HemOnc Today Editorial Board Member. She can be reached at Physician Assistant Studies, 259 Mack Ave., Suite 2590, Detroit, MI 48201; email: mjpilat@wayne.edu.
Disclosure: Pilat reports no relevant financial disclosures.